This grant has for more than a decade provided the core support for a series of studies on patients with primary immunodeficiency syndromes. These patients, as experiments of nature, afford unique opportunities to study specific humoral and cellular immunity as well as non-specific resistance factors in man. Our particular interest has been in defects in antibody formation, assessed by the T-dependent antigen bacteriophage 0x 174. It is our hypothesis that many of the syndromes expressed as defects of humoral immunity, particularly the most common defect, Common Variable Immunodeficiency, reflect abnormalities of helper/suppressor T-cells and associated factors rather than B-cell defects per se. We propose to continue our studies of this problem by monitoring the presence and function of suppressor T-cells, assessing the control mechanisms for immunoglobulin and antibody responses in vivo and in vitro, and by attempting to reconstitute function with modulation of T-cell function by exposure to thymic epithelial monolayers, thymosin and other factors, as well as by transplantation of fetal tissues.